Distinct developmental trajectories of externally and internally generated hippocampal sequences and assemblies

Area of Science:

• Neuroscience
• Developmental Biology
• Cognitive Science

Background:

• The hippocampus creates cognitive maps using external landmarks and internal self-referenced sequences.
• In adult mice, CA1 deep cells process external cues, while superficial cells handle internal representations.
• The developmental timing of these distinct hippocampal functions is currently unknown.

Purpose of the Study:

• To investigate the emergence of internal versus external hippocampal representations during postnatal development.
• To determine the developmental timeline for the formation of cue-based and self-referenced spatial coding in the hippocampus.

Main Methods:

• Longitudinal two-photon calcium imaging was performed in head-fixed mice during the fourth postnatal week.
• Recordings were made from deep and superficial CA1 layers during treadmill running with and without tactile cues.
• Advanced techniques were used to track individual cells across imaging sessions.

Main Results:

• Cue-based (external) representations emerged before internal sequence representations.
• Internal sequences first encoded elapsed time and later integrated running distance.
• The emergence of internal sequences followed the stabilization of spatial coding and functional networks.

Conclusions:

• The fourth postnatal week is a critical period for establishing integrated external and internal hippocampal representations.
• This developmental window is crucial for balanced cognitive map formation.
• Disruptions during this period may increase vulnerability to disorders involving altered cognitive maps.